Cuddly cats, toxoplasma and pregnancy

DCF 1.0
DCF 1.0

A recent case of severe toxoplasma infection in pregnancy at one of my institutions reinforces the need for preconception and early pregnancy hygiene advice.

What is toxoplasma infection?

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. The parasite may be found in raw and cured meat, raw eggs, unpasteurised milk and cat faeces. It can also be found in soil contaminated with cat faeces. This means cat owners need to be careful when they handle kitty litter and should wear gloves when they garden in areas where the soil may be contaminated.

Clinical consequences of toxoplasma infection

Outside of pregnancy, toxoplasmosis results in a mild flu-like illness or a subclinical infection with no symptoms.

However, toxoplasma infection acquired in the period from three months prior to conception and during pregnancy, is more significant.  The parasite can cross the placenta and infect the developing baby who has an immature immune system. The consequences can be serious and include miscarriage, brain damage, blindness and death.

Why the timing of the infection is important

The timing of the infection in pregnancy influences the risk of the baby acquiring the infection. It also impacts on the severity of the sequelae of the infection in the baby.

In early pregnancy, less than 5% of babies are infected. This is because the placenta is too immature for transplacental infection.

However, in late pregnancy, 65% of babies can acquire the infection, as the placenta is mature and rates of transplacental infection are higher.

Even though infection caught late in pregnancy is more likely to result in fetal infection, the consequences of the infection are usually less severe.

In contrast,  infection caught by the mother early in her pregnancy results in a lower fetal infection rate but has far more significant consequences for her baby.

Most of the advice on toxoplasma in pregnancy comes from a few landmark research papers. It is worth looking at the findings from these papers to help guide pregnancy advice and management.

 

 

Landmark research papers

1. Pregnancy outcomes

The first landmark paper on toxoplasma in pregnancy was published in the New England Journal of Medicine in 1974 (1).

The researchers reported on the pregnancy outcomes of two groups of women. One group had evidence of toxoplasmosis prior to pregnancy and the other group acquired toxoplasmosis during pregnancy.

The key findings were:

  • Mothers who acquired toxoplasmosis prior to pregnancy did not infect their baby. No babies in this group had toxoplasmosis.

However;

  • In the 77 women who acquired toxoplasma infection during pregnancy:
    • 11 women miscarried;
    • 7 women suffered fetal death in utero and delivered a stillborn baby;
    • 2 newborns died soon after delivery;
    • 7 babies had severe effects of congenital toxoplasmosis and had cerebral and ocular complications;
    • 11 babies had  only mild illness requiring treatment:
    • 39 babies had subclinical illness with no long term problems.
  • Severe outcomes were only detected when the maternal toxoplasma infection occured during the first two trimesters (up to 27 weeks pregnancy).
  • Acquiring the toxoplasma infection in the third trimester resulted in subclinical infection or in no fetal infection.

2. Risk factors

The largest published research paper on risk factors comes from France (2), which has one of the highest rates of toxoplasma infection in pregnancy in the world. The authors reported that there were approximately 4900 cases of primary Toxoplasma infection in pregnant women in France each year.

Since 1992, France has had a policy that all pregnant women at risk of Toxoplasma infection undergo monthly serological testing. This research paper reported on 80 pregnant women who seroconverted to Toxoplasma in pregnancy and compared their risk factors against 80 pregnant women who had repeatedly negative tests.

After performing a multivariate statistical analysis to ensure differences between the two groups of women were accounted for, they found the risk factors for Toxoplasma infection were:

  • Poor hand hygiene increased risk by almost 10 fold (OR=9.9; 95%CI: 0.8-125);
  • Consumption of undercooked beef increased risk by almost 6 fold (OR=5.5; 95%CI: 1.1-27);
  • Having a pet cat increased risk by almost 5 fold (OR=4.5; 95%CI: 1.0-19.9);
  • Frequent consumption of raw vegetables outside the home increased risk by 3 fold (OR=3.1; 95%CI: 1.2-7.7);
  • Consumption of undercooked lamb increased risk by 3 fold (OR=3.1; 95%CI: 0.85-14).

The researchers noted that when women were provided with documentary advice on how to prevent toxoplasma infection, they had a lower risk of infection. They concluded that all  pregnant women should be given information on their eating habits, hand hygiene and cats in order to reduce the risk of acquiring toxoplasma infection in pregnancy.

3. Treatment of toxoplasma infection in pregnancy

The third landmark paper addressed the treatment of toxoplasma infection in pregnancy (3).

This treatment study was conducted across 5 major centres that specialised in the management of toxoplasma infection in pregnancy. The aim of the study was to determine if prenatal antibiotic therapy could reduce the rate of mother to baby transmission of Toxoplasma gondii and reduce the risk of severe consequences in infected babies as measured when they were one year old.

The study followed 144 women and considered key factors such as the gestational age at which the infection was acquired, the administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy.

The authors reported that 64 of the 144 infected women (44%) gave birth to a congenitally infected infant.

After performing a multivariate analysis they concluded that the rate of transmission from the mother to the baby was not affected by the administration of antibiotics. The only factor that affected the rate of transmission was the gestational age at which the mother developed the infection in pregnancy (P < .0001).

However, antibiotic administration significantly reduced the risk of serious sequelae in the babies (P = 0.026, odds ratio 0.30, 95% confidence interval 0.104-0.863).

Of particular note, severe sequelae were significantly reduced when the mother was administered antibiotics (P = .007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P = 0.021).

The results were consistent with the earlier New England Journal of Medicine paper which also reported that treatment of infected mothers with the antibiotic Spiramycin reduced the impact of fetal infection (1).

What is the current pregnancy advice for preventing toxoplasmosis in pregnancy?

In Australia, the risk of toxoplasma infection is low. Therefore routine screening for the infection is not performed.

The main method to prevent infection is through education on strategies to reduce the risk of becoming infected.

The Australian Government’s Pregnancy, Birth and Baby website outlines strategies to reduce the risk of infection (4). These are:

  • Wear gloves when gardening, particularly when handling soil;
  • Wash your hands thoroughly after handling soil, using soap and hot water;
  • Do not eat raw or undercooked meat;
  • Cook all red meat until no trace of pinkness remains and the juices run clear;
  • Do not eat cured meats (e.g. Parma ham, salami);
  • Do not taste meat before it is fully cooked;
  • Wash your hands thoroughly after handling raw meat;
  • Wash all kitchenware thoroughly after preparing raw meat;
  • Always wash fruit and vegetables before cooking and eating;
  • Avoid drinking unpasteurised goat’s milk or eating products that are made from it;
  • Do not handle or adopt stray cats;
  • Keep animals, especially cats, away from areas that you prepare/store food;
  • Wash your hands and other exposed body parts with soap and running water after touching animals, their enclosures or food containers;
  • Avoid cat faeces in cat litter or soil – wear gloves if you are changing a cat’s litter tray and wash your hands thoroughly afterwards. If you are pregnant or immune deficient, ask someone else to change it for you and empty the litter tray daily;
  • Feed your cat dried or canned cat food rather than raw meat;
  • Cover children’s outdoor sand boxes to prevent cats using them as litter boxes;
  • Avoid contact with sheep and newborn lambs during the lambing season.

Management if infection is suspected

If a pregnant woman is concerned that she may have acquired toxoplasmosis in pregnancy, she should immediately see her doctor or midwife to discuss her concerns and be referred for an antibody test.

If the test demonstrates the presence of IgG antibodies, she can usually be reassured that she has already had the infection and is immune.

If the test demonstrates IgM antibodies, or no antibodies but the clinical suspicion of infection is high, the pregnancy should be managed by an obstetrician with expertise in this area.

Many cases are not detected until an ultrasound examination is performed and is noted to be abnormal.

Once maternal infection is diagnosed, or an ultrasound examination is suspicious of features of toxoplasma infection in the fetus, a tertiary level ultrasound, blood tests and amniocentesis to diagnose fetal infection are indicated. Antibiotic therapy needs to be commenced as soon as possible to reduce the impact of the fetal infection.

All cases should be managed in a tertiary obstetric hospital and advice and management will be individualised to each woman.

Babies should be enrolled in a follow up service to ensure any sequelae are diagnosed and managed as soon as possible.

Summary

Toxoplasma infection in pregnancy resulting in severe consequences for the baby is rare. However it can be prevented with good hygiene practices and managed with expert interventions by specialist teams.

The most important message is to be aware of good hand hygiene practices.

References

  1. Dismounts G, Couvreur J. Congenital Toxoplasmosis — A Prospective Study of 378 Pregnancies.N Engl J Med 1974; 290:1110-1116May 16, 1974. DOI: 10.1056/NEJM197405162902003
  2. Baril L, Ancelle T, Goulet V, Thulliez P, Tirard-Fleury V, Carme B. Risk Factors for Toxoplasma Infection in Pregnancy: A Case-Control Study in France. 
    Scandinavian Journal of Infectious Diseases 1999; 31(3): 305-309. 
    doi.org/10.1080/00365549950163626
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When having a baby can kill you

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Pregnancy is usually a happy time with the outcome being a healthy baby. However, some complications in pregnancy can be serious. Over the years I have cared for many couples with molar pregnancy (technically known as gestational trophoblast disease). This terrible complication of pregnancy not only results in grief from the “lost baby”, but can also have lasting physical, social and psychological consequences for both the mother and father (1,2,3,4). Untreated, molar pregnancy can cause death of the mother (1,2).

Of note, our research into molar pregnancy revealed that many fathers experienced lasting social and psychological symptoms following molar pregnancy (4). One reason for this is due to the origins of the disease.

Origins of molar pregnancy

There are two types of molar pregnancy, a complete mole and a partial mole. In both cases, the male sperm plays a key role.

In a complete molar pregnancy, sperm (one or two) fertilize an egg that has lost its female genetic material (DNA). Therefore all the genetic material in the fertilized egg arises from the male and none from the female.

In a partial molar pregnancy, a single egg is fertilized by two sperm causing an excess of male genetic material within the fertilised egg.

The incidence of molar pregnancy varies around the globe, from 1 in 200 to 1 in 2000 pregnancies (1,2).

Impact on pregnancy

Sadly, molar pregnancy never results in a normal baby except for the extraordinarily rare cases of twinning where one twin is a molar pregnancy and the other a normal pregnancy. Instead, the usual situation is that the uterus becomes full of abnormal placental tissue and no baby is present (complete mole) or some fetal development occurs, but the fetus  is  malformed and not viable (partial mole).

The abnormal placental tissue causes bleeding and can metastasis around to body to other organs such as the lungs, in the same way an untreated cancer may spread around the body.

Impact on women

Most molar pregnancies present with abnormal vaginal bleeding between 8 and 16 weeks of pregnancy. Initially most women are concerned about miscarriage.

The diagnosis may be strongly suspected following an ultrasound, where a characteristic pattern called a “snowstorm” may be seen within the uterus. However, the condition is not definitively diagnosed until a sample of the tissue within the uterus is sent for analysis (histopathology) and tissue that looks like a cluster of grapes (abnormal chorionic villi) are seen under the microscope.

Some women may present with signs of thyroid disease, as the abnormal placental tissue can produce thyroid-like hormones. Women may also present with excessive nausea and vomiting of pregnancy (hyperemesis) and rarely may present with abnormally high blood pressure readings under 20 weeks of pregnancy.

Management of molar pregnancy

Once a molar pregnancy is confirmed, management involves surgery, follow up surveillance and possibly chemotherapy.

The initial management is uterine suction curettage. This surgical procedure is necessary to confirm the diagnosis and exclude an even rarer form of gestational trophoblastic disease called choriocarcinoma. The surgery carries more risk than a usual suction curettage, as the abnormal placental tissue is very vascular, and therefore the risk of heavy bleeding is higher. This means that the attending gynaecologist will often cross match blood and organise an anaesthetic consultation to plan the safest time to perform surgery. Medication may be required following surgery to help contract the uterus and reduce post operative bleeding.

Following surgery, women receive a “risk rating” that is determined on a number of factors such as their levels of pregnancy hormone, blood group, the presence of metastatic disease and the histopathology of the molar pregnancy.

Based on the “risk rating” results, women enter a follow up surveillance program that involves monitoring with serial blood or urine pregnancy hormone levels.

If a women had a high initial risk score, or her pregnancy hormone levels rose or failed to fall during her surveillance period, then she will require chemotherapy. This is usually Methotrexate, but in some case will be combined chemotherapy.

The impact of molar pregnancy on women is often profound. This is particularly true as the risk of molar pregnancy increases as women become older. Some women may have been trying to conceive for many years and then discover their pregnancy is a molar pregnancy. Not only do they not have the baby they desire, they face surgery, prolonged surveillance during which pregnancy is contraindicated, and possible chemotherapy. They must defer trying to have a child until they have been cleared (3,4).

Impact on partners

Partners of affected women can also suffer due to delayed childbearing, prolonged stress and a feeling of guilt related to the male role in the origins of molar pregnancy (4,5,6).

In our research, we contacted 158 former patients in our service with molar pregnancy and through these women, interviewed  41 partners. We found many partners were as emotionally fragile as the woman. For full results click here.

In a thematic analysis we found several themes related to anxiety and fear, sadness and depression, and guilt.

Anxiety

Anxiety was the dominant theme, rather than depression. Anxiety arose in male partners from a sense of frustration consequent to experiencing loss of control over their fertility, particularly their anxiety that they, as a couple, may never have a child.

‘Wouldn’t have occurred to us before when we were just worried about possible health of a baby’

‘Words cannot describe how emotionally stressful it was… I witnessed my partner being torn apart emotionally.’

‘Almost given up hope/plans of having a child at our age (maybe still some fear that another pregnancycould go awry).’

‘My world came crashing down.’

Guilt and blame

Partners felt guilty or blamed themselves for the occurrence of the molar pregnancy. Factors such as the male contribution in conception and individual genetic structures impacted on male participant’s view of cause and effect.

‘I somehow feel responsible in a way that it may have been my fault that it had something to do with my (works) my body that wasn’t right that caused this unusual pregnancy.’

Medical care

Themes relating to medical care centred around the actual treatment of molar pregnancy and the constant reminder of the diagnosis during the prolonged follow up perios that meant couples relived the experience. This delayed emotional recovery. The lack of clear information added to confusion and uncertainty.

‘…we are constantly reminded of our ‘failure’ through monthly urine samples, etc.’

‘I didn’t know as a individual at the time what was going on with my partner because we didn’t have enough information.’

Male partners’ displacement of feelings

Male partners felt a sense of indirect involvement in the management of the molar pregnancy. A new unfamiliar distancing occurred in a small percentage of couple relationships because of withdrawal from communication with partners during this time. This left partners feeling hopeless, unable to initiate appropriate actions to help their partner cope with trauma resulting from the diagnosis.

Partners felt they had to manage other financial and social matters additionally during this period of time. The male partner viewed himself largely as a supporter and made a distinction from being the patient.

‘I still cannot imagine what it would be like for my partner as she was the one carrying the pregnancy.’

‘It is hard for the husband to feel the same sense of loss as the wife because he has not had any physical contact with the “baby”.’

‘I felt very detached from it because it wasn’t my body going through the miscarry.’

Sexual function

Some men reported disparity in sexual functioning with their partner and described sexual tensions in their relationship.

‘My partner seems a little numb now, compared with before, and that makes it harder to feel good about sex and being close. I’m still keen but she seems less so…’

‘With all this happening inside her, she now seems less interested in sex, maybe that’s normal, but when I try she looks almost scared.’

‘…reduced desire by wife/apprehension re. sexual, even sensual contact…’

Positive role of children

The protective effect of children came through in our research. Subsequent delivery of a healthy child overcame the sense of loss.  This was reported both as an actual experience and as a hypothetically positive experience.

‘The scars only really started healing once we were given the gift of a beautiful baby boy nearly 2 years later.’

Summary

Most of the time pregnancy is a happy event, but occasionally things go wrong. It is important to remember that both mother and father may be deeply impacted and to provide support and follow up when things don’t go to plan.

Ultimately, providing support to ensure the couple are able to help each other through a sad and frightening experience is as important as getting the actual medicine right.

 References

  1. Berkowitz RS, Goldstein DP. Gestational trophoblastic diseases. In Principles and Practice of Gynecologic Oncology, Hoskins WJ, Perez CA, Young RC (eds.), Lippincott Williams & Wilkins: Philadelphia, PA, 2000; pp 1117–1137.
  2. Feltman CM, Growden WB, Wolfberg AJ et al. Clinical characteristics of persistent gestational trophoblastic disease after partial hydatidiform molar pregnancy. J Reprod Med 2006;51:902–906.
  3. Berkowitz RS, Marean AR, Hamilton N et al. Psychological and social impact of gestational trophoblastic neoplasia. J Reprod Med 1980;25:14–16.
  4. Quinlivan JA, Ung KA, Petersen RW. The impact of molar pregnancy on the male partner.Psychooncology. 2012 Sep;21(9):970-6. doi: 10.1002/pon.1992. Epub 2011 May 24.
  5. Wenzel L, Berkowitz RS, Robinson S, Bernstein M, Goldstein D. The psychological, social, and sexual consequences of gestational trophoblastic disease. Gynecol Oncol 1992;46:74–81.
  6. Wenzel L, Berkowitz RS, Robinson S, Goldstein DP, Bernstein MR. Psychological, social and sexual effects of gestational trophoblastic disease on patients and their partners. J Reprod Med 1994;39(3):163–167.

Pokemon Go, exercise and gestational diabetes mellitus

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The recent Pokemon Go craze could have an unintentional benefit for women with pregnancy complicated by Gestational Diabetes Mellitus (GDM). The exercise involved in walking  around parks trying to capture Pokemon helps manage blood sugar levels and can lead to a reduced need for medication and diabetic complications.

The benefits of exercise in pregnancy

Regular exercise, particularly walking, is beneficial in pregnancy. Not only can regular exercise limit excessive gestational weight gain to international standards, it can also help prevent or manage GDM (1,2).

However, encouraging women to participate in regular exercise during pregnancy has proven challenging (3). Several randomised trials of exercise interventions in pregnancy have failed to demonstrate an effect on preventing excessive gestational weight gain or on the incidence or management of GDM, mainly due to poor compliance and low levels of participation by pregnant women in exercise programs (3,4,5).

So how might Pokemon Go help?

Women diagnosed with GDM are often asked to monitor their blood sugar level each morning (fasting blood sugar level) and again  2 hours after every meal (post prandial 2 hour blood sugar level). If the morning fasting blood sugar level, or the post prandial 2 hour blood sugar levels are higher than recommended targets (2,5), then medication may be necessary in order to reduce the risk of pregnancy complications such as abnormal fetal growth (macrosomia), excessive amniotic fluid (polyhydramnios), placental damage or fetal death in utero.

Regular exercise, even a 30 minute walk performed three times a week, can be helpful in regulating gestational weight gain and blood sugar levels.

This is where Pokemon Go might help.

By combining a regular walk with a game, it might encourage pregnant women to walk.

Maybe the manufacturers could invent pregnant Pokemon for our pregnant women to capture and provide an extra incentive!

Over to you game makers.

What else is new in gestational diabetes research?

Our research team recently published a paper on managing gestational diabetes (6). In this research study we explored whether it was possible to safely streamline the number of women who have to undergo antenatal investigations.

The particular focus of our recent study was on the value of fetal cardiotocography (CTGs) in managing GDM (6).

Different levels of risk in GDM?

The prevalence of GDM is rising due to increases in maternal obesity and a rise in sedentary lifestyles (6,7,8). If increasing numbers of pregnant women need increasing numbers of tests, our maternity systems will explode and costs of care will rise.

GDM pregnancies do have an increased risk of maternal and fetal complications such as gestational hypertension, pre-eclampsia, caesarean delivery, development of type 2 diabetes postpartum, fetal macrosomia, birth trauma and shoulder dystocia (6,7,8). The risk of maternal and fetal complications is particularly high in GDM pregnancies with poor blood sugar control (6,7,8).

Medications that reduce blood sugar levels in women with GDM include Insulin and Metformin. Medication is only prescribed when women cannot achieve ideal blood fasting and 2-hour post prandial blood sugar levels despite eating a diabetic diet and undertaking regular exercise.

Women who need medication to manage their blood sugar level are therefore  at higher risk of potential pregnancy complications compared to women who are able to manage their blood sugar levels with  diet and exercise.

Fortunately, 70% of women can manage their blood sugar levels with diet and exercise. This means only 30% of women diagnosed with GDM require medication.

Antenatal monitoring in GDM

Antenatal fetal monitoring is routinely performed in pregnancies complicated by GDM.

The two most common tests undertaken to monitor the wellbeing of the fetus are cardiotocographs (CTG) and ultrasound (9,10).

CTG can detect some pregnancies at risk of stillbirth, allowing for prompt further intervention (9,10).

How do CTGs work?

The heart rate of a fetus is determined by a balance between two different types of neurotransmitters (sympathetic and parasympathetic) that  act on the sinoatrial node in the heart (11).

This balance is mediated through a number of factors including catecholamines (11). If fetal pathology is present, and the fetus is unwell, this balance can be affected, and changes in fetal heart rate patterns can be observed on a heart rate trace – the CTG (11,12). 

A number of conditions are associated with abnormal CTG tracings. Specific CTG findings that suggest fetal hypoxia and acidosis include reduced variation in the baseline fetal heart rate and loss of rises in heart rate (accelerations) or development of drops in fetal heart rate after uterine contractions (late decelerations) (13).

Using CTGs in pregnancy complicated with GDM

As high levels of blood sugar can damage the placenta and lead to fetal pathology that makes the fetus at risk of low oxygen or death, CTGs have been used to monitor GDM pregnancies.

However, there is a lack of consensus on the frequency and commencement gestation of CTG monitoring in GDM pregnancies (14,15,16).

Results from our research

In our recent research publication, published in the Australian and New Zealand Journal of Obstetrics and Gynaecology, we evaluated the role of CTGs in managing pregnancy complicated by GDM (6). Click here to read to full paper.

We audited 1404 consecutive antenatal CTGs in women diagnosed with GDM to determine how often they resulted in a change in management.

Overall, we found that in women requiring medication in order to manage their blood sugar levels, 43 CTGs were required to change management.

In women who did not require medication to manage their blood sugar levels, but who had another factor complicating their pregnancy, 161 CTGs were required to change management.

However, in women who did not require medication to manage their blood sugar levels and who had no other pregnancy complication, CTGs did not change management.

Therefore, if pregnant women with GDM can achieve good blood sugar control with changes to their diet and exercise, they do not require CTG monitoring.

This further emphasises the need to promote a diabetic diet and regular exercise in women with GDM.

If Pokemon Go is a potential solution to help encourage pregnant women walk and exercise on a regular basis, then it might result in a cost saving to our health system through improved pregnancy outcomes, less need for prescribed medication in GDM pregnancy and less need for antenatal monitoring with CTGs.

Maybe we should run a trial?

References

  1. Quinlivan J. The Challenge to deliver cost effective care for patients with Gestational Diabetes Mellitus. Repro Syst Sexual Dis 2014; 2014(3):4. DOI: 10.4172/2161-038X.1000144
  2. International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in pregnancy. Diabetes Care 2010;33:676-682.
  3. Quinlivan J Dietary component of lifestyle interventions helps obese pregnant women. Evidence Based Medicine 06/2012; 18:e4 doi:10.1136/eb-2012-100794.
  4. Quinlivan J, Juliania S, Lam L. Antenatal dietary interventions in obese pregnant women to restrict gestational weight gain to institute of medicine recommendations: a meta-analysis. Obstetrics and Gynecology 2011: 118(6): 1395-401.
  5. Nankervis A, McIntyre HD, Moses R, Ross GP, Callaway L, Porter C, et al. Consensus guidelines for the testing and diagnosis of gestational diabetes mellitus in Australia. Australasian Diabetes in Pregnancy Society; 2014.
  6. Jeffery T, Petersen RW, Quinlivan JA. Does cardiotocography have a role in the antenatal management of pregnancy complicated by gestational diabetes mellitus? ANZJOG 2016; DOI: 10.1111/ajo.12487.
  7. Landon MB, Mele L, Spong CY, Ramin SM, Casey B, Wapner RJ, et al. The relationship between maternal glycemia and perinatal outcome. Obstet Gynecol. 2011 Feb;117(2):218-24.
  8. HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991-2002.
  9. Graves CR. Antepartum fetal surveillance and timing of delivery in the pregnancy complicated by diabetes mellitus. Clin Obstet Gynecol. 2007;50(4): 1007-1013.
  10. Kjos SL, Leung A, Henry OA, Victor MR, Paul RH, Medearis AL. Antepartum surveillance in diabetic pregnancies: predictors of fetal distress in labor. Am J Obstet Gynecol. 1995 Nov;173(5):1532-1539.
  11. McDonnell S, Chandraharan E. The Pathophysiology of CTGs and Types of Intrapartum Hypoxia. Current Women’s Health Reviews. 2013;9(3): 158-68.
  12. McDonnell S, Chandraharan E. Fetal Heart Rate Interpretation in the Second Stage of Labour: Pearls and Pitfalls. Br J Med Med Res. 2015;7(12): 957-70.
  13. Devoe LD, Jones CR. Nonstress test: evidence-based use in high-risk pregnancy. Clin Obstet Gynecol. 2002 Dec;45(4):986-992.
  14. Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR, et al. Summary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007 Jul;30(S2) :S251-60.
  15. Landon MB, Vickers S. Fetal surveillance in pregnancy complicated by diabetes mellitus: is it necessary?. J Matern Fetal Neonatal Med. 2002 Dec; 12(6):413-416.
  16. Loomis L, Lee J, Tweed E, Fashner J. What is appropriate fetal surveillance for women with diet-controlled gestational diabetes?. J Fam Pract. 2006 Mar;55(3):238-240.

 

Why you should vaccinate your baby.

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The latest publication from our Australian Father’s Study addressed the subject of infant vaccination (1). Our aim was to explore father’s attitudes. We surveyed 407 Australian men whose partners were in the final trimester of pregnancy, and asked them about their attitude towards infant vaccination.

Overall, 89% had a positive attitude.

However, 9% reported being neutral and 2% expressed a negative attitude towards infant vaccination.

Vaccinations have saved millions of lives

In this modern era we forget about the importance of vaccinations. Many diseases have been eradicated through vaccination. Smallpox is a classic example of a disease now only found in high security laboratories. Yet, Smallpox used to devastate communities causing death and disfigurement.

Ridding the world of Polio

Diseases such as Polio are now also rare. I was in East Timor a decade ago and was privileged to watch a mass vaccination scheme in operation. International funding had been allocated to vaccinate the country against Poliomyelitis.

At the time I was in Aileu, which is one of the 13 administrative districts in East Timor. It was a small district with a population of only  44,325 (Census 2010) and an area of 737 km² (2). The main hospital was located in the district capital, which was also called Aileu (2).

In the week before the vaccination team visited, the local nuns (who ran the public health service at that time), and local hospital staff, had energetically spread the message far and wide for the local populace to attend for vaccination.

On vaccination day, Aileu was a bustling hive of activity. Many families walked or rode on mopeds into the district capital  for vaccination. Entire families lined up to prevent the scourge of Polio.

Polio was a real and present danger in East Timor at that time. I had visited the main hospital in the capital Dili only a few days earlier and had seen two children hospitalised with Poliomyelitis. One was expected to die. Even as an experienced clinician, there is always something soul breaking about seeing a beautiful, cherished young child dying of a disease that could have been prevented by vaccination.

Fortunately, in the case of Polio at least, the private sector (primarily the Bill and Melinda Gates Foundation) and governments have joined forces to promote vaccination and help eradicate this disease.

In 1988, when the Global Polio Eradication Initiative was launched, Polio was present in more than 125 countries and paralyzed about 1,000 children per day (3). Thanks to immunisation efforts, nearly  3 billion children have been immunised against Polio (3).

The impact of the immunisation campaign has been to reduce the number of new cases of Polio by more than 99%. This translates into saving more than 13 million children from paralysis or death.  Today, Polio is found only in Pakistan and Afghanistan, and fewer than 100 cases were reported in 2015. (3)

The need for herd immunity

One critical factor for the success of mass vaccination programs is ‘herd immunity’. Many children still contract vaccine preventable diseases because they were too young to be vaccinated or were unable to receive vaccinations for medical reasons. Unless a sufficient number (critical mass) of people are vaccinated, the disease can still reach our most vulnerable children.

Despite this, some parents choose not to vaccinate their children, citing political, personal or philosophical motives for declining (4-7).

Some parents question the safety, efficacy and necessity of recommended vaccines (4-7).

Australian Father’s opinions on vaccination

So what did our Australian fathers think about vaccination. As stated above, most had a positive attitude and supported vaccination. However, a minority did not.

One key finding in our study was that fathers with neutral or negative attitudes towards infant vaccination considered themselves as having ” significantly higher levels of knowledge of vaccination issues” compared to fathers with positive attitudes to vaccination.  Interestingly, those fathers with neutral or negative attitudes towards vaccination were more likely to have gained their knowledge from the Internet, as opposed to fathers with a positive attitude to vaccinations who gained their knowledge from direct contact with  a healthcare professional.

The comments from some fathers were interesting.

Vaccinations are a medical advance.

Most fathers who had a positive attitude believed vaccinations were a demonstration of the progress of medicine and a sign of an advanced society. One of our fathers said:

“I’m going to make sure my child is vaccinated. When you think back how entire families were wiped out, in the old cemeteries and such, I mean why wouldn’t you vaccinate your child. They are progress.”

Vaccines result in health benefits

Many expectant fathers with a positive attitude felt that vaccinations were essential and saved lives and unvaccinated children were at risk.

“Everyone knows vaccines save lives. Those parents who don’t vaccinate their children put all other children at risk.”

Another father discussed the risk versus benefit of vaccinations:

“The side effects listed are pretty mild – sore arm, irritable for a few hours. The benefits are huge. It can save your child’s life or stop them getting deaf or brain damaged. I know the baby’s not here yet but already I feel very strongly protective. I will do anything to reduce the risk of my child being hurt.”

Anger towards parents who do not vaccinate their children

A common theme expressed by some fathers was anger towards people who did not vaccinate their children because it placed their own child at increased risk.

“I read abut (sic) a baby that died cause a mother took her unvaccinated child to day care. That’s crazy. If not vaccinated you (sic) kid can die. If that happened to me I’d want those parents to pay. Maybe they should go to prison or something because really, they’ve killed that child by their actions.”

This theme was also reflected by expectant fathers with a positive attitude towards vaccination whose partners (the baby’s mother) had a negative attitude. Two participants in this situation wrote detailed comments about their frustration that hospital staff ignored them because the mother’s views carried greater weight. In one case where the mother had signed a “Refusal of vaccination” form the father wrote:

“Why should my child be put at risk because we disagree about this? Why does her opinion matter more than my own? I want Hepatitis B and Vitamin K injections at birth. She thinks they are dangerous. Father’s opinions and values don’t count. We are ignored – even when we are the one saying and doing the right thing and agreeing with the doctors. I was so angry that the midwife ignored me I had to leave the room”

Another father who separated from his partner after enrolling in our study, wrote in his questionnaire:

“She’s bitter about me leaving and taking it out on our baby. She knows I want him to have all the needles and tests. I asked the hospital to give them but they said only the mother can say so. Why is that the case? I mean, why is her word worth more than mine? It’s my baby as much as it is hers. I just want what is best for my baby. She just wants to hurt me.”

Fathers with negative attitudes to vaccination

In the sub-group of fathers with a negative attitude towards vaccination, some fathers stated that the risks of vaccination outweighed benefits. One participant wrote:

“The absolute risk of our child contracting a disease is very low. The risks of vaccination disease such as autism and ADD are high.”

Another participant agreed:

“There are 100s of studies that show a link between vaccines and poor outcomes for children. Papers about autism, nerve damage, immune damage, cancer and death (sic). I mean you risk killing your child just to supposedly keep it safe from disease, but you give it a disease instead. Even if you don’t get a bad event, the needles hurt your child and cause them to suffer.”

Some participants felt that people who conscientiously objected to immunization were being unfairly punished for their choices.

“The government overstate this issue and try to make you feel guilty following your own free will.”

Why vaccination is important

At the end of the day the message is simple.

Vaccines still save lives.

We need enough responsible people in the community to vaccinate their children to protect the vulnerable people within our population. We need enough vaccinated people to ensure we have herd immunity.

No parent should have to lose their child because they were not vaccinated or because other parents decided not to vaccinate their children and create herd immunity.

Vaccination is a social obligation to society.

References

  1. Prosser N, Petersen R, Quinlivan J (2016) Survey of Australian Father’s Attitudes towards Infant Vaccination: Findings from the Australian Father’s Study. Primary Health Care 6: 228. doi:10.4172/2167-1079.1000228
  2. https://en.wikipedia.org/wiki/Aileu_District
  3. http://www.gatesfoundation.org/What-We-Do/Global-Development/Polio
  4. Brown KF, Kroll JS, Hudson MJ, et al. Factors underlying parental decisions about combination childhood vaccinations including MMR: a systematic review. Vaccine. 2010;28(26):4235-4248.
  5. Ramsay ME, Yarwood J, Lewis D, Campbell H, JM. W. Parental confidence in measles, mumps and rubella vaccine: evidence from vaccine coverage and attitudinal surveys. Br J Gen Pract. 2002;52(484):912-916.
  6. Dannetun E, Tegnell A, Hermansson G, Giesecke J. Parents’ reported reasons for avoiding MMR vaccination. A telephone survey. Scand J Prim Health Care. 2005;23(3):149-153.
  7. Gust D, Brown C, Sheedy K, Hibbs B, Weaver D, Nowak G. Immunization attitudes and beliefs among parents: beyond a dichotomous perspective. Am J Health Behav. 2005;29(1):81-92.

Causes and consequences of too many antibiotics in pregnancy

Slide10

Antibiotics in pregnancy

I was recently checking audited hospital files from one of my research trials and noticed the majority of  women had been prescribed an antibiotic in pregnancy. The commonest indication was for prophylaxis against wound infection in women about to have a caesarean section. The second commonest indication was to prevent neonatal group B streptococcal infection in women with vaginal colonisation.

However, many other women had been prescribed antibiotics for urinary tract, vaginal and respiratory infections.

Yet the audit demonstrated that many of the mid stream urine samples and vaginal swabs collected from these women were ultimately normal. The respiratory infections documented in the notes were almost universally viral, and not bacterial.

It seems antibiotics in pregnancy are being overprescribed.

Overprescription of antibiotics in pregnancy

No drug or medication should be taken in pregnancy unless benefit outweighs the risk of harm.

A course of antibiotics prescribed for a viral chest infection or for urinary symptoms when no infection is present, is not harmless. Many patients and obstetric clinical staff mistakenly think it is “safer” to use antibiotics when in doubt.

However, there is a risk of real harm from the overprescription of antibiotics – harm to the mother, baby, and wider community.

Harm to the mother

Every time antibiotics are prescribed, they kill bacteria. However, they kill both harmful and beneficial bacteria.

In pregnancy, the flora of vagina stabilises (1). This stabilisation is associated with improved outcomes in pregnancy.

The use of antibiotics disrupts normal vaginal flora. This is because beneficial bacteria die and this creates an opportunity for pathogenic bacteria to colonise and infect the vagina.  The presence of pathogenic vaginal bacteria in pregnancy has  been linked to many adverse outcomes including preterm birth and fetal death in utero (2,3,4,5).

Colonisation by pathogenic bacteria is not the only risk. Other micro-organisms, such as fungi, can colonise or infect the vagina following a course of antibiotics. One commonly observed complication is post antibiotic vaginal Candidal infection. This can cause symptoms of itch, soreness and vaginal discharge.

Harm to the baby

As a baby is born, it passes through the vagina and acquires microorganisms from the mother’s reproductive tract. When the mother’s vaginal flora is healthy and stabilised, the baby’s microflora in the gastrointestinal tract will also be healthy and stabilise.

However, pathogenic bacteria in the maternal genital tract can be directly transmitted to the baby, causing serious newborn infection.

Even relatively minor pathogens such as Candida can still cause postnatal problems.  Vaginal Candidal infection can result in neonatal oral Candidal infection, and Candidal infection of the maternal nipples. The end result can be breastfeeding and overall feeding difficulties.

Harm to the community

The biggest harm arising from the overprescription of antibiotics comes from the development of resistance.

The Clinical Senate of Western Australia recently hosted a policy debate to develop recommendations to prevent the development and transmission of “Superbugs”. These are bacteria that are resistant to many antibiotics (6).

The World Health Organisation’s 2014 report on global surveillance of antimicrobial resistance reported that antibiotic resistance is no longer a prediction for the future; it is a reality. This year, several bacteria have been identified that are resistant to every known antibiotic.

This is a ticking time bomb for humanity.

Without urgent, coordinated action, the world is heading towards a post-antibiotic era in which common infections and minor injuries, which have been treatable for decades, can once again kill.

Impact of infections and antibiotic resistance

According to the National Health and Medical Research Council (NMHRC) and Australian Commission on Safety and Quality in Healthcare (NSQHS), infection is the most common complication affecting hospital patients, affecting 200,000 patients per year (7). At least half of healthcare associated infections are preventable. Successful infection control to minimise the risk of transmission requires a range of strategies across all levels of the healthcare system and a collaborative approach for successful implementation.

Excess length of stay due to a surgical site infection is between 3.5 and 23 hospital bed days, depending on the type of infection. The total national number of bed days due to surgical site infections for a one year period was estimated to be 206,527 bed days (8). If there was optimal use of antimicrobials and containment of antimicrobial resistance, $300 million of the Australian national healthcare budget could be redirected to more effective use every year (9).

 

What are Superbugs?

Dr Paul Armstrong, Director, Communicable Diseases Control Directorate, Public Health Division, Department of Health WA recently defined Superbugs as being multi-resistant organisms (MROs), resistant to a number of antibiotics. MROs arose from natural selection, that is, evolutionary pressure that selected resistant organisms following exposure to antibiotics within human medicine, veterinary medicine and agriculture.

Dr Armstrong stated the pressure on bacteria to develop resistance occurred in both hospitals (especially large tertiary hospitals) where the sickest patients are cared for and where the need for powerful antibiotics is greatest, and in the community.

Antibiotic resistance organisms are, to some extent, a natural process. However, overuse and misuse of antibiotics accelerates the emergence of drug-resistant strains, so that a drug that was previously effective to treat a particular microorganism is rendered ineffective.

Cost of Superbugs

Dr Armstrong told the Clinical Senate of Western Australia that the USA Centers for Disease Control and Prevention (CDC) estimated that $20 billion in direct costs was associated with antimicrobial resistance each year.

There is a direct cost on the health system due to increased costs of antibiotics, special equipment, prolonged length of stay, increased staff time and tying up of resources.

Some bacteria now had no antibiotics effective against them.

Origins of Superbugs

There are three major sources of Superbugs.

The first is  environmental contamination with antibiotics. This is is a particular problem in developing countries that manufacture pharmaceuticals and where the use of antibiotics in agriculture is not adequately regulated. In some regions, environmental contamination is strong high, multi resistance organisms have been found in the water supply.

The second key driver is unnecessary prescribing of antibiotics. This is a severe problem in the developing world where people are able to access and purchase antibiotics over the counter. However, developed countries also carry some of the blame. It has been estimated that nearly ¾ of all antibiotics in clinical medicine in Australia may have been inappropriately prescribed. This overprescription arises jointly from pressure from patients who overestimate the benefits of antibiotics and also from clinicians who underestimate their harm.

Globalisation was is a third important factor in the emergence and spread of Superbugs. Food imported from countries with higher resistance levels create risk. International travel and medical tourism also drive risk.  Individuals who travel overseas to areas of high antibiotic environmental contamination return to Australia  with infections that are resistant to antibiotics.

What are the solutions to combat Superbugs?

The WA Clinical Senate came up with some solutions to slow the spread of Superbugs. If you are interested in reading the full report and recommendations click here.

However, the two principles are

(a) Prevent antimicrobial resistance from developing in the first place; and

(b) Determine how to manage MROs or Superbugs when they arise.

Strategies for prevention include

  • Good infection control practices;
  • Vaccines;
  • Thorough cleaning practices;
  • Good surveillance systems;
  • Guidelines on appropriate antibiotics use;
  • Screening programs for patients who have been hospitalised within Australia or abroad;
  • Agricultural controls and regulation;
  • Prescription regulation.

At the end of the day, it is  timely to recall the message of the World Health Organization

“Preserve the miracle of antibiotics – “No action today, no cure tomorrow”.

References

  1. Kaakoush NO, Mendz GL, Quinlivan JA. New techniques to characterize the vaginal microbiome in pregnancy. AIMS Microbiology 2016, 2(1);55-68.
  2. Mendz GL, Kaakoush NO, Quinlivan JA Bacterial aetiological agents of intra-amniotic infections and preterm birth in pregnant women. Frontiers in Cellular Infection and Microbiology. 2013, 3: 58. doi: 10.3389/fcimb.2013.00058
  3. Kaakoush N, Quinlivan J, Mendz G. Bacteroides and Hafnia Infections Associated With Chorioamnionitis and Preterm Birth. Journal of Clinical and Gynecological Obstetrics. 06/2014; 3(2):76-79.
  4. Quinlivan JA, Kaakoush NO, Mendz GL. Acinetobacter Species Associated with Spontaneous Preterm Birth and Histological Chorioamnionitis. British Journal of Medicine & Medical Research, 2014; 4(33): 5293-5297.
  5. Mendz GL, Petersen R, Quinlivan JA, Kaakoush NO. Potential involvement of Campylobacter curvus and Haemophilus parainfluenzae in preterm birth. BMJ Case Reports 2014: published online 1 October 2014, doi:10.1136/bcr-2014-205282.
  6. Quinlivan JA, Weeramanthri T, Geelhoed G. Superbugs Executive Summary and recommendations for action from the Clinical Senate of Western Australia. Health Department of Western Australia 2016 March debate.
  7. NHMRC. NHMRC Australian guidelines for the prevention and control of infection in healthcare. canberra NHMRC 2010; 260.
  8. Graves N, Halton K, Robertos L. Costs of health care associated infection. In: Cruickshank M, Fergusson J (ed) Reducing harm to patients from health care associated infection: The role of surveillance. Sydney Australia Commission on Safety and Quality in Health Care 2008, 307-335.
  9. Australia Commission on Safety and Quality in Health Care. Windows into safety and quality in healthcare 2009. Sydney Australia Commission on Safety and Quality in Health Care 2009.

 

 

Week 1 of pregnancy – what happens

Slide02

This is the first in a series of blogs covering the 40 weeks of pregnancy.

The first week of pregnancy occurs during your last menstrual period. The egg and sperm that will eventually join (or fertilise) to become your baby have not yet fully matured.

Therefore, in week 1 of the pregnancy we explore the maturation of the female egg and male sperm, and then briefly review the future home of the pregnancy, the uterus.

Week 1 of pregnancy – The female egg

Interestingly, a woman’s eggs start their life whilst she is herself an unborn baby, within her own mother’s uterus. As many as 20 million eggs begin to form, but most will degenerate before birth.

As the baby girl is first cuddled by her parents, only 700,000 to 2 million eggs remain within the newborn ovaries.

Yet there is further culling. By the time the young girl reaches the cusp of puberty, and has her first menstrual period, only 400,000 eggs remain in the ovaries.

These are the “potential eggs”, the ones capable of responding to the influx of hormones released from the anterior pituitary in the female brain following puberty, that will enable them to mature and possibly be released from the ovary (ovulation – see week 2 for details). The released egg may then be joined with a sperm (fertilisation – see week 3 for details) to begin the pathway of human development.

Week 1 of pregnancy – Recruiting the egg

So how is one particular egg selected from the awaiting 400,000?

Each month, a hormone in the anterior pituitary of the brain called follicle stimulating hormone (FSH) is released. This hormone acts on the ovary and recruits a small batch of eggs from the waiting thousands, and “activates” them.

Why are some eggs selected each month and not others?

We don’t really know.

There are many theories. One theory is that the activated eggs, by random chance, were more advanced than their peers, and had greater capacity to respond to FSH. Maybe they had a better blood supply, more receptors,or more streamlined internal processes. All we know is that every month, a small group of 5-12 eggs respond to FSH and are recruited for the next menstrual cycle.

Competition continues.

Even amongst the activated 5-12 eggs, only one will eventually ovulate. This selected egg, more advanced by random chance, will become the egg available for fertilisation.

Of course, every now and then a few dead heats emerge in the race and two eggs mature at equal rates and are ovulated, paving the way for non identical twins. Rarer still, three or more eggs may ovulate, leading to the birth of triplets and higher order multiples.

Week 1 of pregnancy -The male sperm

Sperm also take a long time to develop, with the process starting at male puberty.

The male testes begin to secrete the hormone testosterone at puberty. The hormone has many effects, one of which is to promote the growth of the testes and the start of spermatogenesis, or the manufacture of sperm.

A mature sperm consists of a head, a mid piece and a tail. The head contains the nuclei with the genetic material that will become the father’s genetic contribution to the new baby. The mid piece contains the “motor” of the sperm, where energy is generated to enable to sperm to swim through the female reproductive tract and fertilise with the egg. The tail of the sperm contains the propulsion system, that enables the sperm to propel forward on its journey.

Spermatogenesis commences at puberty and continues until a man dies. Sperm are produced in waves, which are synchronised. It takes 64 days to develop a mature sperm.

Week 1 of pregnancy – Recruiting the sperm

After being created in the testes, mature sperm are stored in the epididymis, a coiled duct near the testes. During sex, sperm are ejected into the vas deferens, a communicating channel, supplied with nutritious fluids, and then ejaculated.

During a single ejaculation as many as 200 million sperm may be released. However, only a few hundred sperm survive the journey from the upper vagina, through the cervix and uterine cavity and gain entry into the fallopian tube. The fallopian tube is the ultimate destination of the sperm, as it is the site where fertilisation of the female egg will occur.

Interestingly, the final step to mature sperm doesn’t happen in the male. It happens in the female. As sperm enter the fallopian tube, a chemical reaction between the sperm and female fallopian tube secretions change the sperm and it develops the ability to penetrate an egg and fertilise it. This final step is called “Capacitation”.

Sperm are able to survive and fertilise an egg in the fallopian time for 1-3 days after sex.

Week 1 of pregnancy – Within the uterus

In the first week of pregnancy, the women has her period (or menstrual cycle), shedding the uterine lining (endometrium).

Cramps may accompany the bleeding of the menstrual cycle, as arteries in the uterine lining constrict and deprive the lining tissues of oxygen. This process releases chemicals such as prostaglandins, that trigger painful cramps in some women.This is why medication that blocks the actions of prostaglandins, can help the pain and discomfort of menstrual cramps, which in severe cases is called “primary dysmenorrhoea”.

As the first week ends, the arteries in the uterus begin to open and grow again, sending oxygen, nutrients and hormones to enable a new endometrium to grow over the next month.

Week 1 of pregnancy – Summary

In the first week of pregnancy a woman has her period, or menstrual cycle. The old lining of the uterus is shed, and a new lining begins to grow.

In the mother, a hormone called follicle stimulating hormone is released by the brain, and activates a small group of 5-12 eggs within her ovary.

In the father, sperm were created over the preceding 64 days, and are now stored in the epididymus. Of the 200 million sperm may be released during ejaculation. However, only a few hundred will complete the journey from vagina to the fallopian tube, and undergo capacitation, to enable fertilisation of an egg.

For more reading

Brskov AG. Differentiation of the mammalian embryonic gonad. Physiol Rev 1986, 66: 71.

Clermone Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 1972; 52:198.

Larsen WJ. Human Embryology 3rd edition. Churchill Livingston, 2002, Pennsylvania.

Wasserman PM. Elements of mammalian fertilisation Vol 1 Basic concepts 1991, CRC Press, Boca Raton, FL.

Larsen WJ. Human Embryology 3rd edition. Churchill Livingston, 2002, Pennsylvania

40 weeks of pregnancy – overview

IMG_0077When you see your doctor or midwife, they will talk about your pregnancy in terms of “weeks”. Your estimated date of delivery is based on the “40th week”. A term pregnancy is one where the baby is born between “weeks 37 to 42”.

This series within pregnancyandwomenshealth will inform you about the growth and development of your baby in each week of pregnancy.

If you read an embryology textbook things rapidly become complicated. Hopefully this blog will explain development in a simpler way. Then again, maybe not. It really does get complicated at times, especially around weeks 8-20. My colleagues and I have observed many medical and midwifery students develop glazed eyes once we embark on fetal folding. But that comes later. For now, start at week 1 of pregnancy – what happens…